This invention relates generally to the field of bioprosthetic devices, and more particularly to a method and apparatus for in vitro testing of bioprosthetic valves.
In the field of bioprosthetic devices, a wide variety of different aortic valve prostheses have been shown in the prior art. Two main categories of valve prostheses can be defined: mechanical valves, including the so-called xe2x80x9ccaged ballxe2x80x9d, xe2x80x9ccaged discxe2x80x9d, and xe2x80x9ctilting discxe2x80x9d types; and tissue valves, which have leaflets. Of the various aortic valve prostheses currently known, the mechanical valves tend to be more circumferentially rigid than tissue valves. Tissue valves are typically stented and tend to be more or less circumferentially rigid, depending upon the rigidity of the stent.
It is believed by the inventors, however, that valves less rigid than even the current stented tissue valves would be preferable in some cases since they more closely simulate a natural aortic valve and would therefore be less likely to create problems in the patient with unfavorable systolic and diastolic turbulence patterns, systolic pressure gradients, or embolic episodes. Further, it is believed that compliant bioprosthetic valves, having qualities more closely matched to natural aortic valves, would tend to have better flow efficiency, superior hydraulic characteristics, and flow patterns that are significantly less trauma-promoting and less likely to produce such undesirable effects as thrombus, atherosclerosis, or hemolysis.
The possibility of fatigue-related or other failure of the valve or leaflets has necessitated rigorous stress analysis and testing of bioprosthetic valves. Typically, the development of a bioprosthetic valve involves several iterations of the following steps: (1) fabrication of prototypes in various sizes; (2) in vitro (fluid-mechanical, structural, and fatigue) testing of the prototypes; and (3) refinement and re-fabrication.
Among the more common tests are: steady flow studies, which focus on the pressure gradients across the valves; pulsatile flow studies, which are concerned with valve dynamics (opening and closing times, leaflet motion, and the like), forward and backward (regurgitating) flow patterns, the pressure gradients across the valve, and energy loss across the valve; and fatigue studies, which are concerned with the ability of the valve to withstand millions of cycles without fatigue-related failure. These are discussed extensively in the literature.
Of course, it is important for the conditions of any in vitro testing of bioprosthetic devices to simulate, as closely as possible, the in vivo conditions to which the tested devices will be exposed upon implant in patients. In the case of mechanical valves and stented tissue valves, it is a simple matter to rigidly dispose a valve prosthesis, which is itself circumferentially rigid, along a fluid flow path for the purposes of testing. In conventional practice, a stented valve is fitted into a rigid valve holder and secured in place therein by means of a threaded retaining ring. The entire circumferentially rigid valve and valve holder can then be easily introduced into the flow path of various types of testing equipment.
It has been the inventors"" experience that in the case of a non-stented valve, it is substantially more difficult to provide a fixture for introducing the non-stented tissue valve into a flow path during in vitro testing that, while providing support for the valve attachment to the tester, does not interfere with the physiological functioning of the valve. In particular, it is believed to be desirable to provide a test fixture for non-stented bioprosthetic valves which does not restrict the circumferential compliance of the valve, so that the effects of the valve""s compliant circumferential expansion and contraction of the valve can be observed and monitored during the in vitro testing.
In addition, in vitro evaluation of non-stented aortic bioprostheses requires that the valve be mounted in a test chamber that reasonably simulates the human aortic root. The use of a simulated or synthetic aortic root has been proposed in the prior art. Artificial aortic roots have been discussed, for example, in Reul et al., xe2x80x9cOptimal Design of Aortic Leaflet Prosthesisxe2x80x9d, American Society of Civil Engineers, Journal of the Engineering Mechanics Division, v. 104, n. 1, February 1978, pp. 91-117; in Ghista et al., xe2x80x9cOptimal Prosthetic Aortic Leaflet Valve: Design Parametric and Longevity Analyses: Development of the Avcothane 51 ,Leaflet Valve Based on the Optimum Design Analysisxe2x80x9d, Journal of Biomechanics, 10/5-6, 1977 pp 313-324; and in Lu et al., xe2x80x9cMeasurement of Turbulence in Aortic Valve Prostheses: An Assessment by Laser Doppler Anemometerxe2x80x9d, Proceedings of a Symposium at the 14th Annual Meeting of the Association for the Advancement of Medical Instrumentation, Las Vegas, Nev. May 21, 1979, Yoganathan et al., editors. The foregoing Reul et al., Ghista et al., and Lu et al. references are incorporated herein by reference in their entirety. Such aortic roots have been made of polyurethane and silicone rubber.
In developing a simulated aorta for in vitro use, several factors must be considered. First, the aortic valve in its natural state does not have a fixed shape, and can only be described at a given time in the cardiac cycle, such as mid-systole or mid-diastole. Second, the human aorta is anisotropic and expands quite easily at low internal pressure but stiffens at higher pressures to prevent ballooning (this is discussed in Thubrikar et al., xe2x80x9cNormal Aortic Valve Function in Dogsxe2x80x9d, American Journal of Cardiology, vol. 40, October 1977; in Brewer et al., xe2x80x9cThe Dynamic Aortic Rootxe2x80x9d, Journal of Cardiovascular Surgery, Jun. 3, 1976; and in Ferguson et al., xe2x80x9cAssessment of Aortic Pressure-Volume Relationships With an Impedance Catheterxe2x80x9d, Catheterization and Cardiovascular Diagnosis, 15:27-36, 1988). The foregoing Thubrickar et al., Brewer et al., and Ferguson et al. references incorporated herein by reference in their entirety. The compliance may vary with age and with disease states.
Finally, since in vitro evaluation of an aortic bioprosthesis requires extended testing, a material which provides bacterial stability is necessary. Materials such as rubber provide bacterial stability and can be easily produced to exact geometric dimensions, but these materials are isotropic and do not exhibit the same locking characteristics at high pressures that are seen with anisotropic materials. For these reasons, it would be advantageous to provide a simulated aorta of repeatable geometric design and having controllable compliance characteristics to provide reasonable in vitro models of natural aortas.
With the in vitro testing arrangement proposed by Lu et al. in the above-cited reference, the compliance factor for a flow loop system including a simulated aortic root is provided not by the simulated root itself, but rather by means of a compliance chamber disposed on the outflow side of the valve being tested. It would be desirable to provide the necessary compliance in the aorta itself for better simulation of the natural aorta.
In the above-cited Reul et al. and Ghista et al. references, the artificial aortic root is made from polyurethane by a dipping process, so that the desired compliance is achieved by controlling the thickness of the polyurethane at the time the artificial aorta is fabricated. (The Reul et al. flow loop additionally contains a compliance element for approximating natural compliance factors during testing.) The lack of consistency in the thickness of the root may pose difficulties. The trial and error effort required to develop aortas of the desired compliance would require large numbers of molds of different thicknesses, all very expensive to make, resulting in a very expensive, possibly a prohibitively expensive, development effort for valves produced commercially. Furthermore, the geometry (i.e., the thickness) of the simulated aorta will vary with each level of compliance so that test results performed at one compliance level may not be able to be accurately compared to those at other compliance levels.
In one aspect, the invention is a method of creating a simulated aorta patterned from a natural aorta and having a preselected amount of compliance comprising the following steps:
selecting the dimensions of a simulated aortic root patterned according to the dimensions of a natural aorta;
providing a mold for a simulated aorta of the desired dimensions;
selecting the amount of circumferential compliance desired in the simulated aorta;
selecting a material of appropriate durometer to provide the selected amount of circumferential compliance in a simulated aorta having the selected dimensions; and
making the aorta by curing the material in the mold.
In this aspect, the material is preferably a polymer comprising an elastomer and a filler and the durometer of the material results from varying the proportions of the filler and the elastomer.
In another aspect, the invention is a group of simulated aortas prepared according to the above method, preferably comprised of materials of different Durometers so that the aortas have at least two different compliancies. Each aorta may have dimensions sized to receive one valve in a group of prosthetic valves of different sizes.
In another aspect, the invention is a method of testing non-stented valves comprising the following steps:
selecting the dimensions of a simulated aortic root patterned according to the dimensions of a natural aorta;
selecting the amount of circumferential compliance desired in the simulated aorta;
selecting a material of appropriate durometer to provide the selected amount of circumferential compliance in a simulated aorta having the selected dimensions;
making the aorta of the given dimensions by curing the material, and;
placing a non-stented tissue valve having an outer diameter about the same size as the inner diameter of the simulated aorta within the aorta, and
using the valve and aorta to test the performance of the valve to determine whether it can be recommended for use.
In this aspect, the method preferably includes the step of selecting the dimensions for simulated aortic roots of more than one size, the step of selecting the material includes the step of varying the durometer of a two-component material, and the testing step includes the step of testing more than one valve, each valve having the dimensions of a simulated aorta.
Other aspects and embodiments of the invention will be apparent to those of ordinary skill in the art.